摘要
目的:探索 miRNA-148a 在膀胱癌发生发展中的作用。方法收集35例膀胱癌组织和16例非癌组织,采用荧光定量 PCR 方法检测 miRNA-148a 的相对表达量,并分析其与临床特征的相关性;采用生物信息学分析,预测 miRNA-148a的靶基因和转录因子,构建 TF-miRNA-148a-靶基因调控网络图,并对其靶基因进行 GO 富集和 KEGG Pathway 分析。结果miRNA-148a 在膀胱癌中的相对表达量(0.0008±0.0002)明显低于非癌组织(0.0021±0.0005)(t=2.46,P <0.05),其相对表达量在不同性别、年龄、病理分级、临床分期、淋巴结转移组的差异无统计学意义(P >0.05)。3个软件都预测到的 miRNA-148a 靶基因268个;预测到 miRNA-148a 的转录因子60个,结合评分>80的结合位点657个;对268个靶基因进行 GO 富集分析,发现其靶基因主要涉及神经细胞分化、发育、增殖、mRNA 合成,蛋白连接等众多的生物学过程(P <0.001,相对于背景具有统计意义);KEGG Pathway 分析发现268个靶基因参与 p53,恶性肿瘤、前列腺癌、PI3K-AKT 等信号通路(P <0.05,相对于背景具有统计意义);根据构建的 TF-miRNA-148a-靶基因调控网络图,挖掘出可能调控 miRNA-148a 的转录因子有 SP1,ESR1,AP1,MYC,BRCA1等;可能受 miRNA-148a 调控的基因有 IGF1,P27 kip1,NCOA1,PTEN, SERPINE1等。结论miRNA-148a 在膀胱癌中表达下调,可能参与膀胱癌的发生发展,生物信息学分析为后续研究提供一定的思路。
Objective To explore the role of miRNA-148a in bladder tumorous development and progression.Methods Ex-pression of miRNA-148a was assessed in 35 bladder carcinoma tissues and 16 non-carcinoma tissues by fluorescence quanti-tative real time PCR,and correlation with clinical features was evaluated.Target genes and transcription factors of miRNA-148a were predicted using bioinformatic analysis,then TF-miRNA-148a-target genes network diagram was built and the tar-get genes was analyzed of gene ontology enrichment and KEGG pathway.Results Expression of miRNA-148a was lower in bladder carcinoma tissues than in non-carcinoma tissues(0.000 8±0.000 2 vs 0.002 1±0.000 5)(t=2.46,P 〈0.05),but its expression was no statistical significance in different groups of gender,age,pathological classification,clinical stage, lymph node metastasis (P 〉0.05).268 target genes of miRNA-148a were predicted by three softwares at the same time,60 transcription factors were predicted and the binding sites with combination scroes above 80 was 657.The target genes of miRNA-148a was enriched in many biological processes,such as neuron differentiation,generation of neurons,neuron projec-tion development,cytoplasmic mRNA processing body,cytoplasm(P 〈0.001).They also participated in p53 signaling path-way,proteoglycans in cancer-homo sapiens,pathways in cancer,prostate cancer,protein processing in endoplasmic reticulum, focal adhesion and so on(P 〈0.05).According to TF-miRNA-148a-target genes network diagram,miRNA-148a was regula-ted by SP1,ESR1,AP1,MYC and BRCA1,genes of IGF1,P27kip1 ,NCOA1,PTEN,SERPINE1 might be regulated by miR-NA-148a.Conclusion miRNA-148a which was significantly down-regulation in bladder carcinoma tissues may be participate in bladder tumorous development and progression,bioinformatics analysis provides some ideas for further research.
出处
《现代检验医学杂志》
CAS
2015年第4期6-9,13,共5页
Journal of Modern Laboratory Medicine
基金
国家自然科学基金面上项目(81372151).